Department of Nephrology, Heidelberg University Hospital, Heidelberg, Germany.
Transplantation. 2011 Apr 15;91(7):779-85. doi: 10.1097/TP.0b013e31820d3b9b.
Efficacy and safety of an intensified dosing (ID) regimen of enteric-coated mycophenolate sodium (EC-MPS), which achieves higher mycophenolic acid exposure early posttransplantation, were evaluated in comparison with a standard dosing (SD) regimen.
In total, 128 de novo kidney transplant recipients treated with basiliximab induction, cyclosporine A, and steroids were randomized (1:1) to receive EC-MPS as SD (1440 mg/day; n=65) or ID (days 0-14: 2880 mg/day; days 15-42: 2160 mg/day; followed by 1440 mg/day; n=63). Efficacy parameters, safety, and tolerability were assessed over a 6-month study period. The primary endpoint was mean time to first occurrence of treatment failure.
Mean time to treatment failure was 130 days (95% confidence interval [CI]: 81-n/a) in the ID group versus 114 days (95% CI: 15-155) in the SD group (P=0.36). Similar percentages (ID 30.2%; SD 36.9%) experienced treatment failure. Biopsy-proven acute rejection occurred in 2 (3.2%) ID versus 11 (16.9%) SD patients (P<0.001). Three (2.3%) deaths (2 SD, 1 ID) and five (3.9%) graft losses (3 SD, 2 ID) occurred. Renal function, incidence of infection, and hematologic disorders were comparable in both study cohorts. Gastrointestinal disorders occurred in 51 (81.0%) ID and 49 (75.4%) SD patients with overall similar tolerability as assessed by the Gastrointestinal Symptom Rating Scale.
In this exploratory study, the EC-MPS ID regimen reduced the incidence of rejection and showed a comparable safety and tolerability profile to SD. Further examination of this approach in a larger patient cohort is now warranted to confirm these findings.
与标准剂量（SD）方案相比，强化剂量（ID）方案的肠溶剂型麦考酚酸钠（EC-MPS）在移植后早期实现更高的麦考酚酸暴露，其疗效和安全性已得到评估。
总共 128 例接受巴利昔单抗诱导、环孢素 A 和类固醇治疗的初治肾移植受者随机（1:1）接受 EC-MPS 治疗，SD 方案（1440mg/天；n=65）或 ID 方案（天 0-14：2880mg/天；天 15-42：2160mg/天；随后 1440mg/天；n=63）。在 6 个月的研究期间评估了疗效参数、安全性和耐受性。主要终点是首次治疗失败的平均时间。
ID 组的平均治疗失败时间为 130 天（95%置信区间[CI]：81-无/n/a），SD 组为 114 天（95%CI：15-155）（P=0.36）。相似比例（ID 组 30.2%；SD 组 36.9%）发生治疗失败。活检证实的急性排斥反应分别发生在 2 例（3.2%）ID 患者和 11 例（16.9%）SD 患者中（P<0.001）。3 例（2.3%）死亡（2 例 SD，1 例 ID）和 5 例（3.9%）移植物丢失（3 例 SD，2 例 ID）。两组患者的肾功能、感染发生率和血液系统疾病相当。胃肠道疾病分别发生在 51 例（81.0%）ID 患者和 49 例（75.4%）SD 患者中，通过胃肠道症状评分量表评估，总体耐受性相似。
在这项探索性研究中，EC-MPS ID 方案降低了排斥反应的发生率，并且具有与 SD 方案相当的安全性和耐受性。现在需要在更大的患者队列中进一步检查这种方法，以确认这些发现。
